This invention relates to modulation of ocular development and, more particularly, to induction of axial elongation of the eye.
At age 6 months, the human eye is about two-thirds adult size and is even at that size relatively short in the axial direction. As a consequence, young children tend to be farsighted. During childhood, as the eye grows, there is a compensatory fine tuning of the optical properties of the cornea and lens to an increasing ocular length. Often the entire process is virtually perfect: no accommodation is needed for sharp vision at distance; the eye is emmetropic. Regulatory failure in this finely tuned process can go in either direction. If it goes toward a lengthened eye, then distant images focus in front of the plane of the retina and axial myopia results. If, on the other hand, the regulatory failure leads to an eye whose ocular length is too short, distant images would focus behind the plane of the retina and the result is hyperopia or farsightedness.
An eye that is axially shorter than average by a small amount and as a consequence hyperopic by a small amount, up to about 2.0 Diopters, is usually of little clinical consequence, except for the need for glasses in the adult. However, hyperopia of more than 2.0 Diopters often requires optical correction even in childhood. In addition, it can lead to problems. For instance it can be accompanied by squint (as it presents in children) due to a well described synergism between the internal focusing and external converging systems of the eye. In effect, the constant demand for focussing power stimulates excess convergence and one eye turns in. This form of hyperopia often requires correction by eyeglasses in early life. The small eye of hyperopia can bring problems in early or later life as well. After age 40 it can be subject to an acute form of glaucoma as a steady increase in lens size (the lens normally grows in anterior-posterior diameter steadily through life) crowds the iris too far forward toward the cornea and thus blocks the outflow pathway for aqueous humor.
Prior work leading to the present invention is scant and only indirectly related, as it concerns:
1) the discovery of an experimental model of myopia induced by deprivation of form vision, usually to one eye. Prior work on visual form deprivation includes: PA1 2) the discovery that axial eye growth is responsive to the imposition of plus or minus power lenses for a developing eye. A lens that brings the image plane forward retards axial elongation and one that moves the image back enhances axial eye elongation. One example is supplied by the work of Schaeffel, F., et al., J. Optical Soc. of America, 5: 2080, (1988).
The discovery by Weisel & Raviola, "Myopia and Eye Enlargement After Neonatal Lid Fusion in Monkeys", Nature 266:66 (1977), that the form deprived monkey eye enlarges in the axial dimension and becomes myopic;
U.S. Pat. No. 5,055,302, to Laties and Stone, discloses a method of inhibiting the abnormal postnatal growth of the eye of a maturing animal using vasoactive intestinal peptide (VIP), PH1 or analogues of these peptides. These peptides were found to inhibit axial elongation of a visually deprived myopic eye;
U.S. Pat. No. 5,122,522, to Laties and Stone, discloses a method of inhibiting the abnormal postnatal growth of the eye of a maturing animal using pirenzepine. Axial elongation of a myopic eye was inhibited upon application of pirenzepine; and
In a clear departure from the vision form deprivation work, the present invention derives from experiments in chicks that are not visually manipulated in any way; that instead have both eyes open from birth and are permitted unimpaired vision. The present invention discloses a method to enhance the growth of a developing eye in the axial dimension. Also, axial elongation by cholinergic agonists is found to be inhibited by cholinergic antagonists and dopamine agonists.